EU/3/02/088: Orphan designation for the treatment of Pseudomonas aeruginosa lung infection (including colonisation) in cystic fibrosis

Chronic infection of the lung with the bacterium Pseudomonas aeruginosa represents a hallmark of cystic fibrosis. It can induce damage to the lung tissue and respiratory insufficiency, which is life threatening.

At the time of designation, Pseudomonas aeruginosa lung infection in cystic fibrosis affected approximately 1.3 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 49,000 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP).

* The number of patients affected by the condition is estimated and assessed for the purpose of the designation, for a European Community population of 377,000,000 (Eurostat 2001) and may differ from the true number of patients affected by the condition. This estimate is based on available information and calculations presented by the sponsor at the time of the application.

Pseudomonas aeruginosa lung infection in cystic fibrosis is treated predominantly with antibiotic therapy administered by a variety of routes, oral, intravenous and as an aerosol via nebulisation. Several antibiotics had been authorised for the condition in some countries in the Community, at the time of submission of the application for orphan designation. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that colistimethate sodium might be of potential significant benefit for the treatment of Pseudomonas aeruginosa lung infection in cystic fibrosis, particularly in terms of its low potential for resistance and its ease of administration as a dry powder inhalation.

Colistimethate is an antibiotic produced by certain strains of bacteria. The sponsor has developed a formulation for dry powder inhalation to be administered with a commercial device. In contrast to many antibiotics, which target specific molecules in the bacteria, colistimethate is claimed to have a “physical” mechanism of action disrupting the bacterial membrane. This action cannot be countered by the resistance mechanisms employed by bacteria against other antibiotics with specific cellular enzyme targets, resulting in a very low degree of resistance to colistimethate.

At the time of the submission of the application for orphan designation clinical trials with colistimethate sodium dry powder inhaler in cystic fibrosis patients with Pseudomonas aeruginosa lung infection had not been initiated.

Colistimethate sodium dry powder inhaler had not been marketed anywhere worldwide for this condition or designated as an orphan medicinal product elsewhere, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 18 December 2001 recommending the granting of this designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the Community) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.